This study aimed to investigate the common molecular mechanism between obesity and papillary thyroid cancer (PTC), the most common pathological type of thyroid cancer. In this study, we obtained gene expression datasets for obesity (GSE151839) and PTC (GSE33630) from the Gene Expression Omnibus (GEO). We used the Perl program and R software to identify differentially expressed genes (DEGs) and common genes, perform GO function and KEGG pathway enrichment analysis, construct a protein-protein interaction (PPI) network, identify hub genes, and perform transcription factors (TFs) analysis. After undergoing validation in external datasets and in vitro experiments, common targets for both diseases were ultimately identified. A total of 23 genes that were differentially expressed (DEGs) between obesity and papillary thyroid carcinoma (PTC) were identified in our study. Among these DEGs, 17 genes were up-regulated while 6 genes were down-regulated. Then the top ten key genes were identified from the PPI network using cytoHubba and MCODE plug-in. Further evidence from external datasets revealed that MMP9, MNDA, TNC, and CHIT1 were identified as hub genes for both diseases. The study utilized Transcriptional Regulatory Relationships Unraveled by Sentence-based Text mining (TRRUST) to perform an enrichment analysis of TFs. This analysis identified ELF4 and STAT3 as common TFs for both diseases. Additionally, in vitro experiments were conducted to further analyze the clinical significance and biological functions of these TFs. The identification and investigation of hub genes and their corresponding TFs that regulate abnormalities in obesity and PTC can enhance our comprehension of the underlying connection between these two diseases, thus leading to the development of novel diagnostic approaches.